The economic burden of asthma and chronic obstructive pulmonary disease and the impact of poor inhalation technique with commonly prescribed dry powder inhalers in three European countries.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are common chronic inflammatory respiratory diseases, which impose a substantial burden on healthcare systems and society. Fixed-dose combinations (FDCs) of inhaled corticosteroids (ICS) and long-acting ß2 agonists (LABA), often administered using dry powder inhalers (DPIs), are frequently prescribed to control persistent asthma and COPD. Use of DPIs has been associated with poor inhalation technique, which can lead to increased healthcare resource use and costs. METHODS: A model was developed to estimate the healthcare resource use and costs associated with asthma and COPD management in people using commonly prescribed DPIs (budesonide + formoterol Turbuhaler(®) or fluticasone + salmeterol Accuhaler(®)) over 1 year in Spain, Sweden and the United Kingdom (UK). The model considered direct costs (inhaler acquisition costs and scheduled and unscheduled healthcare costs), indirect costs (productive days lost), and estimated the contribution of poor inhalation technique to the burden of illness. RESULTS: The direct cost burden of managing asthma and COPD for people using budesonide + formoterol Turbuhaler(®) or fluticasone + salmeterol Accuhaler(®) in 2015 was estimated at €813 million, €560 million, and €774 million for Spain, Sweden and the UK, respectively. Poor inhalation technique comprised 2.2-7.7 % of direct costs, totalling €105 million across the three countries. When lost productivity costs were included, total expenditure increased to €1.4 billion, €1.7 billion and €3.3 billion in Spain, Sweden and the UK, respectively, with €782 million attributable to poor inhalation technique across the three countries. Sensitivity analyses showed that the model results were most sensitive to changes in the proportion of patients prescribed ICS and LABA FDCs, and least sensitive to differences in the number of antimicrobials and oral corticosteroids prescribed. CONCLUSIONS: The cost of managing asthma and COPD using commonly prescribed DPIs is considerable. A substantial, and avoidable, contributor to this burden is poor inhalation technique. Measures that can improve inhalation technique with current DPIs, such as easier-to-use inhalers or better patient training, could offer benefits to patients and healthcare providers through improving disease outcomes and lowering costs.

Observation of the decay B- → D(s)((*)+) K- ℓ- ν(ℓ).

We report the observation of the decay B- → D(s)((*)+) K- ℓ- ν(ℓ) based on 342 fb(-1) of data collected at the Υ(4S) resonance with the BABAR detector at the PEP-II e+ e- storage rings at SLAC. A simultaneous fit to three D(s)(+) decay chains is performed to extract the signal yield from measurements of the squared missing mass in the B meson decay. We observe the decay B- → D(s)((*)+) K- ℓ- ν(ℓ) with a significance greater than 5 standard deviations (including systematic uncertainties) and measure its branching fraction to be B(B- → D(s)((*)+) K- ℓ- ν(ℓ)) = [6.13(-1.03)(+1.04)(stat)±0.43(syst)±0.51(B(D(s)))]×10(-4), where the last error reflects the limited knowledge of the D(s) branching fractions.

Search for f(J)(2220) in radiative J/ψ decays.

We present a search for f(J)(2220) production in radiative J/ψ→γf(J)(2220) decays using 460 fb⁻¹ of data collected with the BABAR detector at the SLAC PEP-II e(+)e⁻ collider. The f(J)(2220) is searched for in the decays to K(+)K⁻ and K(S)°K(S)°. No evidence of this resonance is observed, and 90% confidence level upper limits on the product of the branching fractions for J/ψ→γf(J)(2220) and f(J)(2220)→K(+)K⁻(K(S)°K(S)°) as a function of spin and helicity are set at the level of 10⁻5, below the central values reported by the Mark III experiment.

Search for charged lepton flavor violation in narrow upsilon decays.

Charged-lepton flavor-violating processes are unobservable in the standard model, but they are predicted to be enhanced in several extensions to the standard model, including supersymmetry and models with leptoquarks or compositeness. We present a search for such processes in a sample of 99x10(6)Upsilon(2S) decays and 117x10(6)Upsilon(3S) decays collected with the BABAR detector. We place upper limits on the branching fractions B(Upsilon(nS)-->e(+/-)tau(-/+)) and B(Upsilon(nS)-->mu(+/-)tau(-/+)) (n=2,3) at the 10(-6) level and use these results to place lower limits of order 1 TeV on the mass scale of charged-lepton flavor-violating effective operators.

Test of lepton universality in Υ(1S) decays at BABAR.

The ratio R(τµ)(Υ(1S))=Γ(Υ(1S)→τ+ τ-)/Γ(Υ(1S)→µ+ µ-) is measured using a sample of (121.8±1.2)×10(6)Υ(3S) events recorded by the BABAR detector. This measurement is intended as a test of lepton universality and as a search for a possible light pseudoscalar Higgs boson. In the standard model (SM) this ratio is expected to be close to 1. Any significant deviations would violate lepton universality and could be introduced by the coupling to a light pseudoscalar Higgs boson. The analysis studies the decays Υ(3S)→Υ(1S)π+ π-, Υ(1S)→l+ l-, where l=µ, τ. The result, R(τµ)(Υ(1S))=1.005±0.013(stat)±0.022(syst), shows no deviation from the expected SM value, while improving the precision with respect to previous measurements.

Evidence for direct CP violation in the measurement of the Cabbibo-Kobayashi-Maskawa angle γ with B∓ → D(*)K(*)∓ decays.

We report the measurement of the Cabibbo-Kobayashi-Maskawa CP-violating angle γ through a Dalitz plot analysis of neutral D-meson decays to K(S)(0) π+ π- and K(S)(0) K+ K- produced in the processes B∓ → DK∓, B∓ D* K∓ with D* → Dπ(0), Dγ, and B∓ → DK*∓ with K*∓ → K(S)(0) π∓, using 468 million BB pairs collected by the BABAR detector at the PEP-II asymmetric-energy e+ e- collider at SLAC. We measure γ = (68 ± 14 ± 4 ± 3)° (modulo 180°), where the first error is statistical, the second is the experimental systematic uncertainty, and the third reflects the uncertainty in the description of the neutral D decay amplitudes. This result is inconsistent with γ = 0 (no direct CP violation) with a significance of 3.5 standard deviations.

Measurements of charged current lepton universality and |Vus| using tau lepton decays to e- ν(e) ν(τ), µ- ν(µ) ν(τ), π- ν(τ), and K- ν(τ).

Using 467 fb(-1) of e+e- annihilation data collected with the BABAR detector, we measure (B(τ- → µ- ν(µ) ν(τ)))/(B(τ- → e- ν(e) ν(τ))) =(0.9796±0.0016±0.0036), (B(τ- → π- ν(τ)))/(B(τ- → e- ν(e) ν(τ))) = (0.5945±0.0014±0.0061), and (B(τ- → K- ν(τ)))/(B(τ- → e- ν(e) ν(τ))) = (0.03882±0.00032±0.00057), where the uncertainties are statistical and systematic, respectively. From these precision τ measurements, we test the standard model assumption of µ-e and τ-µ charge current lepton universality and provide determinations of |Vus| experimentally independent of the decay of a kaon.

Measurement of D0-D0 mixing parameters using D0 → K(S)(0)π+ π- and D0 → K(S)(0)K+ K- decays.

We report a direct measurement of D0-D0 mixing parameters through a time-dependent amplitude analysis of the Dalitz plots of D(0) → K(S)(0) π+ π- and, for the first time, D0 → K(S)(0)K+ K- decays. The low-momentum pion π(s)(+) in the decay D*+ → D0 π(s)(+) identifies the flavor of the neutral D meson at its production. Using 468.5 fb(-1) of e+ e- colliding-beam data recorded near square root(s)=10.6 GeV by the BABAR detector at the PEP-II asymmetric-energy collider at SLAC, we measure the mixing parameters x = [1.6 ± 2.3(stat) ± 1.2(syst) ± 0.8(model)] × 10(-3), and y = [5.7 ± 2.0(stat) ± 1.3(syst) ± 0.7(model)] × 10(-3). These results provide the best measurement to date of x and y. The knowledge of the value of x, in particular, is crucial for understanding the origin of mixing.

Measurement of |V(cb)| and the form-factor slope in B --> Dl- nu(l) decays in events tagged by a fully reconstructed B meson.

We present a measurement of the Cabibbo-Kobayashi-Maskawa matrix element |V(cb)| and the form-factor slope rho2 in B --> Dl- nu(l) decays based on 460x10(6) BB events recorded at the Upsilon(4S) resonance with the BABAR detector. B --> Dl- nu(l) decays are selected in events in which a hadronic decay of the second B meson is fully reconstructed. We measure B(B- --> D0 l- nu(l))/B(B- --> Xl- nu(l)) = (0.255+/-0.009+/-0.009) and B(B0 --> D+ l- nu(l))/B(B0 --> Xl- nu(l)) = (0.230+/-0.011+/-0.011), along with the differential decay distribution in B --> Dl- nu(l) decays. We then determine G(1)|V(cb)| = (42.3+/-1.9+/-1.4)x10(-3) and rho2 = 1.20+/-0.09+/-0.04, where G(1) is the hadronic form factor at the point of zero recoil.

Searches for Lepton flavor violation in the decays tau{+/-}-->e{+/-}gamma and tau{+/-}-->mu{+/-}gamma.

Searches for lepton-flavor-violating decays of a tau lepton to a lighter mass lepton and a photon have been performed with the entire data set of (963+/-7)x10{6} tau decays collected by the BABAR detector near the Upsilon(4S), Upsilon(3S) and Upsilon(2S) resonances. The searches yield no evidence of signals and we set upper limits on the branching fractions of B(tau{+/-}-->e{+/-}gamma)<3.3x10{-8} and B(tau{+/-}-->mu{+/-}gamma)<4.4x10{-8} at 90% confidence level.

Long-term radiographic appearance of a bioabsorbable biocomposite tibial tuberosity advancement cage implant.

OBJECTIVE: To report the radiographic appearance of a bioabsorbable biocomposite tibial tuberosity advancement cage at least 1 year after implantation. Design Retrospective case series. METHODS: Medical records (February 2014-March 2015) of dogs receiving a biocomposite tibial tuberosity advancement cage were reviewed. Cases were selected if they had undergone surgery at least 1 year before the selection, no additional surgeries were performed, and no known surgical site infection had occurred. Medical record information assessed included signalment, body weight (kg), affected stifle joint (left or right), date of original surgery and the size of biocomposite cage used (9 or 12 mm). Radiographs were evaluated by two blinded radiologists who calculated percentages of osteolucency present in five zones around the cage and assigned a numerical score based on these calculations. Variables were evaluated statistically for effect on lucency percentage and numerical score. RESULTS: Fifty dogs were included. Zone 5 (caudoproximal area) was found to have the lowest lucency percentage and score and zone 3 (distal area) had the highest lucency percentage and score. Twelve-millimetre cages were significantly associated with a higher lucency numerical score than 9 mm cages. CONCLUSION: A biocomposite tibial tuberosity advancement cage was found to have variable amounts of radiographically apparent osseous integration at least 1 year after implantation.

Measurement of D{0}-D[-over]{0} mixing from a time-dependent amplitude analysis of D{0}-->K+pi{-}pi{0} decays.

We present evidence of D{0}-D[-over ]{0} mixing using a time-dependent amplitude analysis of the decay D{0}-->K+pi{-}pi;{0} in a data sample of 384 fb{-1} collected with the BABAR detector at the PEP-II e+e{-} collider at the Stanford Linear Accelerator Center. Assuming CP conservation, we measure the mixing parameters x{Kpipi{0}}{'}=[2.61{-0.68}{+0.57}(stat)+/-0.39(syst)]%, y{Kpipi;{0}}{'}=[-0.06{-0.64}{+0.55}(stat)+/-0.34(syst)]%. This result is inconsistent with the no-mixing hypothesis with a significance of 3.2 standard deviations. We find no evidence of CP violation in mixing.

Measurement of B-->K{*}(892)gamma branching fractions and CP and Isospin asymmetries.

We present an analysis of the decays B{0}-->K{*0}(892)gamma and B{+}-->K{*+}(892)gamma using a sample of about 383 x 10{6} BB[-over ] events collected with the BABAR detector at the PEP-II asymmetric energy B factory. We measure the branching fractions B(B{0}-->K{*0}gamma)=(4.47+/-0.10+/-0.16) x 10{-5} and B(B{+}-->K{*+}gamma)=(4.22+/-0.14+/-0.16) x 10{-5}. We constrain the direct CP asymmetry to be -0.033K{*}gamma)<0.028 and the isospin asymmetry to be 0.017

Precise measurement of the e+e- --> pi+pi-(gamma) cross section with the initial state radiation method at BABAR.

A precise measurement of the cross section of the process e(+)e(-) --> pi(+)pi(-)(gamma) from threshold to an energy of 3 GeV is obtained with the initial state radiation (ISR) method using 232 fb(-1) of data collected with the BABAR detector at e(+)e(-) center-of-mass energies near 10.6 GeV. The ISR luminosity is determined from a study of the leptonic process e(+)e(-) --> mu(+)mu(-)gamma(gamma). The leading-order hadronic contribution to the muon magnetic anomaly calculated using the pipi cross section measured from threshold to 1.8 GeV is (514.1 +/- 2.2(stat) +/- 3.1(syst)) x 10(-10).

Search for invisible decays of the Upsilon(1S).

We search for invisible decays of the Upsilon(1S) meson using a sample of 91.4 x 10(6) Upsilon(3S) mesons collected at the BABAR/PEP-II B factory. We select events containing the decay Upsilon(3S) --> pi(+)pi(-)Upsilon(1S) and search for evidence of an undetectable Upsilon(1S) decay recoiling against the dipion system. We set an upper limit on the branching fraction B(Upsilon(1S) --> invisible) < 3.0 x 10(-4) at the 90% confidence level.

Evidence for the eta(b)(1S) meson in radiative Upsilon(2S) decay.

We have performed a search for the eta_{b}(1S) meson in the radiative decay of the Upsilon(2S) resonance using a sample of 91.6x10(6) Upsilon(2S) events recorded with the BABAR detector at the PEP-II B factory at the SLAC National Accelerator Laboratory. We observe a peak in the photon energy spectrum at Egamma=609.3(-4.5)(+4.6)(stat)+/-1.9(syst) MeV, corresponding to an eta(b)(1S) mass of 9394.2(-4.9)(+4.8)(stat)+/-2.0(syst) MeV/c2. The branching fraction for the decay Upsilon(2S)-->gamma(eta)b(1S) is determined to be [3.9+/-1.1(stat)-0.9+1.1(syst)]x10(-4). We find the ratio of branching fractions B[Upsilon(2S)-->gamma(eta)b(1S)]/B[Upsilon(3S)-->gamma(eta)b(1S)]=0.82+/-0.24(stat)(-0.19)(+0.20)(syst).

Search for a low-mass higgs boson in Upsilon(3S)-->gammaA(0), A(0)-->tau(+)tau(-) at BABAR.

We search for a light Higgs boson A0 in the radiative decay Upsilon(3S)-->gammaA(0), A(0)-->tau+tau-, tau+-->e+nu(e)nu(tau), or tau+-->mu+nu(mu)nu(tau). The data sample contains 122x10(6) Upsilon(3S) events recorded with the BABAR detector. We find no evidence for a narrow structure in the studied tau+tau- invariant mass region of 4.03gammaA(0))xB(A(0)-->tau+tau-)>(1.5-16)x10(-5) across the m(tau+tau-) range. We also set a 90% C.L. upper limit on the tau+tau- decay of the eta(b) at B(eta(b)-->tau+tau-)<8%.

Search for the rare decay B-->pil+ l-.

We have performed a search for the flavor-changing neutral-current decays B-->pil+ l-, where l+ l- is either e+ e- or mu+ mu-, using a sample of 230 x 10(6) Upsilon(4S)-->BB decays collected with the BABAR detector. We observe no evidence of a signal and measure the upper limit on the isospin-averaged branching fraction to be B(B-->pil+ l-)<9.1 x 10(-8) at 90% confidence level. We also search for the lepton-flavor-violating decays B-->pie+/- mu-/+ and measure an upper limit on the isospin-averaged branching fraction of B(B-->pie+/- mu-/+)<9.2 x 10(-8) at 90% confidence level.

Budesonide + formoterol delivered via Spiromax® for the management of asthma and COPD: The potential impact on unscheduled healthcare costs of improving inhalation technique compared with Turbuhaler®.

BACKGROUND: Fixed-dose combinations of inhaled corticosteroids and long-acting ß2 agonists are commonly used for the treatment of asthma and COPD. However, the most frequently prescribed dry powder inhaler delivering this medicine - Symbicort® (budesonide and formoterol, BF) Turbuhaler® - is associated with poor inhalation technique, which can lead to poor disease control and high disease management costs. A recent study showed that patients make fewer inhaler errors when using the novel DuoResp® (BF) Spiromax® inhaler, compared with BF Turbuhaler®. Therefore switching patients from BF Turbuhaler® to BF Spiromax® could improve inhalation technique, and potentially lead to better disease control and healthcare cost savings. METHODS: A model was developed to estimate the budget impact of reducing poor inhalation technique by switching asthma and COPD patients from BF Turbuhaler® to BF Spiromax® over three years in Germany, Italy, Sweden and the UK. The model estimated changes to the number, and associated cost, of unscheduled healthcare events. The model considered two scenarios: in Scenario 1, all patients were immediately switched from BF Turbuhaler® to BF Spiromax®; in Scenario 2, 4%, 8% and 12% of patients were switched in years 1, 2 and 3 of the model, respectively. RESULTS: In Scenario 1, per patient cost savings amounted to €60.10, €49.67, €94.14 and €38.20 in Germany, Italy, Sweden and the UK, respectively. Total cost savings in each country were €100.86 million, €19.42 million, €36.65 million and €15.44 million over three years, respectively, with an estimated 597,754, 151,480, 228,986 and 122,368 healthcare events avoided. In Scenario 2, cost savings totalled €8.07 million, €1.55 million, €2.93 million and €1.23 million over three years, respectively, with 47,850, 12,118, 18,319, and 9789 healthcare events avoided. Savings per patient were €4.81, €3.97, €7.53 and €3.06. CONCLUSIONS: We demonstrated that reductions in poor inhalation technique by switching patients from BF Turbuhaler® to BF Spiromax® are likely to improve patients' disease control and generate considerable cost savings through healthcare events avoided.

Measurements and analysis of fluid saturation-dependent NMR relaxation and linebroadening in porous media.

NMR T1, T2 and spectral linewidth measurements were conducted in rock samples with different saturations obtained by drainage experiments. Saturation dependent T1 was found to follow a power-law relationship and the inverse of linewidth to follow a linear dependence with saturation. These phenomena can be explained by considering that the fluids are distributed in different sized pores for different saturation states. A method is proposed for calculating wetting phase relative permeabilities using T1 data at various saturations.